Immunological challenge modulates brain orphanin FQ/nociceptin and nociceptive behavior |
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Authors: | Kawashima Noriko Fugate Jean Kusnecov Alexander W |
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Institution: | Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan. yamada@ncnp.go.jp |
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Abstract: | Neuromedin B (NMB) is a mammalian bombesin-like peptide distributed widely in the central nervous system. This peptide exerts its function via the NMB receptor (NMB-R). Female NMB-R-deficient mice were used to study the role that NMB/NMB-R may play in 5-HT neuron function since this relationship was suggested in previous in vitro studies. As 5-HT neurons are thought to modulate marble burying behavior, a role for NMB-R in this behavior was assessed. Relative to wild-type mice, NMB-R-deficient mice showed decreased marble burying behavior. However, depletion of 5-HT by treatment with p-chlorophenylalanine (p-CPA) increased burying behavior in NMB-R-deficient mice suggesting that increased levels of 5-HT in the brain cause a decrease in burying behavior in NMB-R-deficient mice. While HPLC analysis showed that 5-HT content in the whole brain does not differ between NMB-R-deficient and wild-type mice, an immunohistochemical analysis of brain sections showed that 5-HT expression in the dorsal raphe (DR) nucleus is elevated in NMB-R-deficient mice. Furthermore, a quantitative RT-PCR analysis revealed that 5-HT(1A)-receptor gene expression is downregulated in NMB-R-deficient mice at the whole brain level. These behavioral and biological results suggest that NMB/NMB-R may modulate 5-HT neuronal activity by affecting DR function. |
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Keywords: | Neural-immune interaction Orphanin FQ Nociceptin Hyperalgesia Immune system Cytokine LPS Staphylococcal enterotoxin A |
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